This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie COFUND grant agreement No 665735.

Bio4Med Research Projects:


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14: Bio4Med - Development and evaluation of metabolic multimodality therapies against neurological tumors based on arginine deprivation

Supervisor:
prof. Maria Jolanta Redowicz
Foreign partner:
Dr Oleh V. Stasyk, Institute of Cell Biology NASU, Lviv, Ukraine
WWW
http://en.nencki.gov.pl/laboratory-of-molecular-basis-of-cell-motility
Background:
The project rationale is based on our novel observation that lack of arginine profoundly and selectively impaired motility, adhesion and invasiveness of three different human glioblastoma cells lines and showed that these effects were due to specific alterations in the actin cytoskeleton organization caused by impaired β-actin arginylation (Pavlyk et al., 2015, Amino Acids 47:199-212). In the planned study all relevant modern methodological approaches will be used: confocal and fluorescence microscopy for cell morphology; assays evaluating autophagy and the cytoskeleton organization; Western blotting for apoptosis markers; cytometry for cell viability assays, as well as assays probing cell motility/migration, adhesion and invasiveness.
Aim:
We would like to test whether neurological cancers can be potential targets of arginine deprivation-based enzymotherapy, and specifically, we would like to: - evaluate sensitivity of model brain tumor cell lines (glioblastoma and neuroblastoma) to combinational treatment of arginine deprivation with (i) drugs affecting the microtubule cytoskeleton; (ii) autophagy and proteasome inhibitors; (iii) amino acid analogues selectively toxic for tumor cells; and (iv) drugs affecting cells energy metabolism; - identify drugs which exhibit additive or synergetic effects with arginine deprivation on tumor cells viability/metastatic potential, and those for which arginine deprivation significantly decreases the effective dose.; - investigate the molecular mechanism(s) of tumor cells death under the chosen multimodality treatment and to formulate a proposal for animal study.
Requirements:
The candidate should have a strong background in modern cell biology techniques aforementioned. He/she should have strong determination in solving scientific problems, high motivation and a good knowledge of English. Since the candidate during the project realization will spend at least three months in the laboratory of the Ukrainian partner, at least minimal command of Ukrainian would be an asset. Persons with a previous laboratory experience are especially encouraged to apply. Candidates must not have resided or carried out their main activity (work, studies, etc.) in Poland for more than 12 months in the past 3 years.